Causal associations between female reproductive behaviors and psychiatric disorders: a lifecourse Mendelian randomization study.

BACKGROUND: The timings of reproductive life events have been examined to be associated with various psychiatric disorders. However, studies have not considered the causal pathways from reproductive behaviors to different psychiatric disorders. This study aimed to investigate the nature of the relationships between five reproductive behaviors and twelve psychiatric disorders. METHODS: Firstly, we calculated genetic correlations between reproductive factors and psychiatric disorders. Then two-sample Mendelian randomization (MR) was conducted to estimate the causal associations among five reproductive behaviors, and these reproductive behaviors on twelve psychiatric disorders, using genome-wide association study (GWAS) summary data from genetic consortia. Multivariable MR was then applied to evaluate the direct effect of reproductive behaviors on these psychiatric disorders whilst accounting for other reproductive factors at different life periods. RESULTS: Univariable MR analyses provide evidence that age at menarche, age at first sexual intercourse and age at first birth have effects on one (depression), seven (anxiety disorder, ADHD, bipolar disorder, bipolar disorder II, depression, PTSD and schizophrenia) and three psychiatric disorders (ADHD, depression and PTSD) (based on p<7.14×10-4), respectively. However, after performing multivariable MR, only age at first sexual intercourse has direct effects on five psychiatric disorders (Depression, Attention deficit or hyperactivity disorder, Bipolar disorder, Posttraumatic stress disorder and schizophrenia) when accounting for other reproductive behaviors with significant effects in univariable analyses. CONCLUSION: Our findings suggest that reproductive behaviors predominantly exert their detrimental effects on psychiatric disorders and age at first sexual intercourse has direct effects on psychiatric disorders.

Low Expression of GIGYF1 Inhibits Metastasis, Proliferation, and Promotes Apoptosis and Autophagy of Gastric Cancer Cells.

GRB10 interacting GYF protein 1 (GIGYF1) binds to the N-terminal region of Grb10, regulates multiple signaling pathways. However, it is not clear what happens to cell proliferation, metastasis, apoptosis, and autophagy when the expression level of GIGYF1 gene is reduced. Detection of GIGYF1 expression in clinical tissue specimens and gastric cancer (GC) cell lines by quantitative Real-time PCR (qRT-PCR), GIGYF1 gene was knocked down in MGC-803 cells using small interfering RNA, the effect of GIGYF1 gene on cell metastasis was detected using Transwell assay and wound healing assay, the effect on cell proliferation was detected using plate cloning assay and cck-8 assay, the effect on apoptosis was detected using flow cytometry, autophagosomes were detected using laser confocal microscopy, and the effect on protein expression was detected using immunofluorescence and Western blotting. GIGYF1 gene expression was higher in tumor tissue samples than in paracancer tissue samples, and higher in human GC cell lines than in human normal gastric epithelial cells. GIGYF1 gene knockdown inhibited cell migration, scratch healing ability and EMT process, weakened cell proliferation ability, increased apoptosis rate, promoted the formation of autophagosomes, and changed the corresponding protein expression level. Meanwhile, GIGYF1 knockdowns inhibited the ERK and AKT signaling. In conclusion, the low expression of GIGYF1 gene can inhibit the occurrence and progression of gastric cancer, during which the ERK and AKT signaling pathways are inhibited.

Development and Validation of a Bayesian Network-Based Model for Predicting Coronary Heart Disease Risk From Electronic Health Records.

BACKGROUND: Traditional risk evaluation models have been applied to guide public health and clinical practice in various studies. However, the application of existing methods to data sets with missing and censored data, as is often the case in electronic health records, requires additional considerations. We aimed to develop and validate a predictive model that exhibits high performance with data sets that contain missing and censored data. METHODS AND RESULTS: This is a retrospective cohort study of coronary heart disease at Weihai Municipal Hospital on unique patients aged 18 to 96 years between 2013 and 2021. A total of 169 692 participants formed our study population, of which 10 895 participants were diagnosed with coronary heart disease. Models were built for the risk of coronary heart disease based on demographic, laboratory, and medical history variables. All complete samples were assigned to the training set (n=110 325), whereas the remaining samples were assigned to the validation set (n=59 367). The area under the receiver operating characteristic curve value was 0.800 (95% CI, 0.794-0.805), and the C statistic was 0.796 (95% CI, 0.791-0.801) in the derivation cohort, and the corresponding values were 0.837 (95% CI, 0.821-0.853) and 0.838 (95% CI, 0.822-0.854) in the validation cohort. The calibration curve demonstrated its good calibration ability, and decision curve analysis showed its clinical usefulness. CONCLUSIONS: Our proposed risk prediction model has demonstrated significant effectiveness in handling the complexities of electronic health record data, which often involve extensive missing data and censoring. This approach may offer potential assistance in the use of electronic health records to enhance patient outcomes.

Helicobacter pylori regulates stomach diseases by activating cell pathways and DNA methylation of host cells.

One of the most prevalent malignant tumors of the digestive tract is gastric cancer (GC). Age, high salt intake, Helicobacter pylori (H. pylori) infection, and a diet deficient in fruits and vegetables are risk factors for the illness. A significant risk factor for gastric cancer is infection with H. pylori. Infecting gastric epithelial cells with virulence agents secreted by H. pylori can cause methylation of tumor genes or carcinogenic signaling pathways to be activated. Regulate downstream genes' aberrant expression, albeit the precise mechanism by which this happens is unclear. Oncogene, oncosuppressor, and other gene modifications, as well as a number of different gene change types, are all directly associated to the carcinogenesis of gastric cancer. In this review, we describe comprehensive H. pylori and its virulence factors, as well as the activation of the NF-κB, MAPK, JAK/STAT signaling pathways, and DNA methylation following infection with host cells via virulence factors, resulting in abnormal gene expression. As a result, host-related proteins are regulated, and gastric cancer progression is influenced. This review provides insight into the H. pylori infection, summarizes a series of relevant papers, discusses the complex signaling pathways underlying molecular mechanisms, and proposes new approach to immunotherapy of this important disease.

Association between dietary habits and the risk of migraine: a Mendelian randomization study.

Objective: The important contribution of dietary triggers to migraine pathogenesis has been recognized. However, the potential causal roles of many dietary habits on the risk of migraine in the whole population are still under debate. The objective of this study was to determine the potential causal association between dietary habits and the risk of migraine (and its subtypes) development, as well as the possible mediator roles of migraine risk factors. Methods: Based on summary statistics from large-scale genome-wide association studies, we conducted two-sample Mendelian randomization (MR) and bidirectional MR to investigate the potential causal associations between 83 dietary habits and migraine and its subtypes, and network MR was performed to explore the possible mediator roles of 8 migraine risk factors. Results: After correcting for multiple testing, we found evidence for associations of genetically predicted coffee, cheese, oily fish, alcohol (red wine), raw vegetables, muesli, and wholemeal/wholegrain bread intake with decreased risk of migraine, those odds ratios ranged from 0.78 (95% CI: 0.63-0.95) for overall cheese intake to 0.61 (95% CI: 0.47-0.80) for drinks usually with meals among current drinkers (yes + it varies vs. no); while white bread, cornflakes/frosties, and poultry intake were positively associated with the risk of migraine. Additionally, genetic liability to white bread, wholemeal/wholegrain bread, muesli, alcohol (red wine), cheese, and oily fish intake were associated with a higher risk of insomnia and (or) major depression disorder (MDD), each of them may act as a mediator in the pathway from several dietary habits to migraine. Finally, we found evidence of a negative association between genetically predicted migraine and drinking types, and positive association between migraine and cups of tea per day. Significance: Our study provides evidence about association between dietary habits and the risk of migraine and demonstrates that some associations are partly mediated through one or both insomnia and MDD. These results provide new insights for further nutritional interventions for migraine prevention.

Comparative efficacy and safety of glucose-lowering drugs in children and adolescents with type 2 diabetes: A systematic review and network meta-analysis.

Objective: Type 2 diabetes is more common in adults, but is becoming the major concern in children and adolescent recently. This study aimed to provide additional pharmaceutical management for children and adolescents with type 2 diabetes by assessing the efficacy and safety of several glucose-lowering drugs. Methods: Searches were performed in PubMed, Medline, Ovid, Cochrane Controlled Register of Trials (CENTRAL), and ClinicalTrials.gov that reported the efficacy and safety of drugs for children and adolescents with type 2 diabetes. Pooled effects were calculated by frequentist fixed effects network meta-analyses and additive network meta-analyses. Results: A total of 12 trials assessing eight glucose-lowering drugs were included, which compose of seven trials with monotherapy and five trials with combination therapies. Network meta-analysis results showed compared to placebo, saxagliptin+metformin (mean difference (MD) -1.91% [-2.85%, -0.97%]), liraglutide+metformin (MD -1.45% [-1.65%, -1.26%]), and liraglutide (MD -0.90% [-1.35%, -0.45%]) were the top 3 drugs that significantly reduced hemoglobin A1c (HbA1c). Sitagliptin+metformin, dapagliflozin, exenatide-2mcg, linagliptin-5mg, metformin, exenatide-5/10mcg, glimepiride, and sitagliptin also showed significant reduction in HbA1c. There were no significant differences between treatments in the incidence of adverse events, except that liraglutide+metformin had significant adverse effect such as abdominal pain. In addition, dapagliflozin, sitagliptin+metformin, and saxagliptin+metformin showed better efficacy compared with FDA-approved drugs. Conclusions: The top 10 treatments of type 2 diabetes in children and adolescents aged 10-17 years were saxagliptin+metformin, liraglutide+metformin, liraglutide, dapagliflozin, exenatide-2 mcg, sitagliptin+metformin, linagliptin-5 mg, linagliptin-1 mg, metformin, and exenatide-5/10 mcg. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=284897, identifier CRD42021284897.

Mechanism of Different Stereoisomeric Astaxanthin in Resistance to Oxidative Stress in Caenorhabditis elegans.

As a potent antioxidant in human diet, astaxanthin (AST) may play important roles in alleviating oxidative stress-driven adverse physiological effects. This study examined the effects of different stereoisomers of AST in protecting Caenorhabditis elegans from chemically induced oxidative stress. Three stereoisomers of AST investigated herein included 3S,3´S (S) AST, 3R,3´R (R) AST, and a statistical mixture (S: meso: R = 1:2:1) (M) AST. Under paraquat-induced oxidative conditions, all three types of AST significantly enhanced survival rate of C. elegans. The accumulation levels of ROS in the worms were reduced by 40.12%, 30.05%, and 22.04% by S, R, and M AST, respectively (P < 0.05). Compared with R and M AST, S significantly enhanced the expression levels of SOD-3. The results of RNA-Seq analysis demonstrated that AST protected C. elegans from oxidative damage potentially by modulating genes involved in the insulin/insulin-like growth factor (IGF) signaling (IIS) pathway and the oxidoreductase system. It is noteworthy that different stereoisomers of AST showed different effects on the expression levels of various genes related with oxidative stress. This study revealed important information on the in vivo antioxidative effects of AST stereoisomers, which might provide useful information for better utilization of AST.